Case Presentation: A 25-year-old Black transgender woman receiving cross-sex hormone therapy (CSHT) with a PMH of multiple hospitalizations for HbSS sickle cell disease (SCD) complicated by acute chest syndrome, chronic left upper extremity DVT, and painful vaso-occlusive crises (VOC) was admitted for acute back and leg pain. She described the pain as constant, sharp, 10/10 severity, and consistent with prior VOC. Vitals were stable throughout admission. On exam, she appeared uncomfortable with diffuse tenderness of the lumbar and lower extremity musculature and joints. There was no swelling, erythema, deformity, weakness, or loss of sensation. Labs showed WBC 17,600/µL and Hb 6.7 g/dL (baseline 7.0 g/dL). Chest x-ray was unremarkable (Image 1). Initial treatment included transfusion of one unit pRBC, IV morphine and diphenhydramine with symptomatic improvement. Leukocytosis resolved and Hb returned to baseline without further transfusions. VOC pain was managed with non-opioid medications and morphine PCA, which was converted to oral oxycodone prior to discharge.
Discussion: Multiple studies have shown that SCD and exogenous estrogen use independently increase the risk of thromboembolic events. However, while extensive data is available on VOC frequency in the general SCD population, including a meta-analysis of 52 studies published in Orphanet Journal of Rare Diseases in 2021, the incidence of VOC with estrogen CSHT remains unknown. Our transgender patient suffered frequent vaso-occlusive complications of SCD while receiving CSHT for male-to-female transition, requiring nine hospitalizations in one year. In risk-benefit discussions regarding hypothetical increased risk for VOC with CSHT, her consistent choice was to continue CSHT as a priority in maintaining her self-identity and quality of life.Additionally, limited data is available to guide the management of SCD in transgender women. A Letter to the Editor published in the American Journal of Hematology in 2018 acknowledged the complexities and significance of SCD in transgender females. Nonadherence to SCD-modifying therapy in the presence of stroke history precluded one of their patients from receiving adequate doses of CSHT, and she relied on non-prescribed estrogen supplementation to obtain feminization of features. For another patient, CSHT was discontinued due to frequent SCD complications including recurrent PE and VOC. Otherwise, the literature addressing SCD patients receiving estrogen therapy have involved ethinyl estradiol use in cisgender women; these data cannot be effectively extrapolated to transgender women because 17-β estradiol, not ethinyl estradiol, is used for CSHT.
Conclusions: More investigation is warranted regarding the frequency of VOC in SCD patients, including analysis of comparable morbidity within specific subpopulations such as transgender SCD patients. The correlation between estrogen CSHT and incidence of VOC in female transgender patients with SCD remains unclear. This case report intends to spread awareness of this important population of high-risk individuals for which providers must advocate. Consequences of decisions surrounding medical therapy for transgender patients with SCD are far-reaching, intertwined with self-identity and strongly influence quality of life.
